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Biomedical subjects

D M Jones

Publications and source records attributed to D M Jones.

At least 91 records · Page 5Linked to original sources
PubMed1993

Engraftment of human synovium into severe combined immune deficient mice. Migration of human peripheral blood T cells to engrafted human synovium and to mouse lymph nodes.

To determine the feasibility of using the C.B-17 scid/scid (severe combined immune deficient, SCID) mouse as a recipient of human synovial xenografts, we have engrafted human synovium under the renal capsule of SCID mice, and determined synovial graft survival and histologic characteristics 4 to 7 wk after tissue implantation. Both normal and inflammatory synovial tissue grew well in SCID mice and maintained histologic and phenotypic components of the fresh synovial tissue before implantation. However, the number of T cells in synovial grafts decreased after implantation. To determine whether leukocytes could migrate to human synovial xenografts, either allogenic or autologous PBMC were injected in the peritoneum of SCID mice bearing synovial xenografts. We found that 7 days after i.p. injection of autologous or allogeneic PBMC, injected T cells had selectively migrated to human synovial grafts and to SCID mouse lymph nodes. Our data demonstrate that normal and inflammatory human synovial tissues will grow in SCID mice and serve as recipients for autologous and allogenic peripheral blood human T cells injected i.p. into engrafted mice.

Aged↗
PubMed1993

Meningococcal infections in England and Wales: 1992.

Fewer cases of meningococcal infection were identified in England and Wales during 1992 than in 1991. The 1301 isolates received by the PHLS Meningococcal Reference Unit represented a decrease of 7%, continuing the trend of the last two years. Most regions saw a reduction in cases, but increased numbers of isolates were received from some regions, notably Northern (up 22%), East Anglia (up 25%) and South West Thames (up 50%). Group C infections (down 17%) contributed disproportionately to the decrease; the numbers of isolates of this organism being the lowest since 1986. Serology is a reliable diagnostic method in cases where no isolate is obtained.

Adolescent↗
PubMed1993

Induction of HIVMN neutralizing antibodies in primates using a prime-boost regimen of hybrid synthetic gp120 envelope peptides.

We have tested synthetic peptides composed of Th (T1) and V3 loop B cell neutralizing determinants [SP10 MN(A)] of HIVMN gp120 and the fusogenic (F) domain of gp41 as immunogens in rhesus monkeys. After two immunizations with either HIV env peptide T1-SP10 MN(A) or F-T1-SP10 MN(A), rhesus monkey serum neutralization titers against the HIVMN isolate ranged from 1:160 to 1:1400, and in cell-cell syncytium inhibition assay ranged from 1:20 to 1:80. However, in contrast to animals immunized with T1-SP10 MN(A), animals immunized twice with F-T1-SP10 MN(A) had no rise in anti-gp120 and neutralizing antibodies with an additional immunization with F-T1-SP10 MN(A) peptide. One of 4 rhesus monkeys (18987) had anti-HIVMN antibodies that cross-neutralized divergent HIV isolates HIVIIIB and HIVRF. Serum from animal 18987 neutralized 5 of 10 HIV isolates tested, and neutralizing activity against HIVIIIB of 18987 serum was absorbed with the conserved gp120 loop V3 sequence IGPGRAF. Anti-HIV neutralizing antibodies were boosted after a 6-mo rest by 500 micrograms of T1-SP10 MN(A) in 4 of 4 animals previously immunized with T1-SP10 MN(A) and in 2 of 2 animals previously immunized with F-T1-SP10 MN(A). However, immunization after 6-mo rest of animal 18987 with 500 micrograms of T1-SP10 MN(A) peptide, although boosting anti-HIVMN neutralizing antibodies, selectively did not boost cross-neutralizing anti-HIVIIIB antibodies. Thus, synthetic peptides containing T and B cell epitopes of HIV gp120 can induce high levels of anti-HIVMN neutralizing antibodies in primates.

Amino Acid Sequence↗
PubMed1993

Conversion of an immunogenic human immunodeficiency virus (HIV) envelope synthetic peptide to a tolerogen in chimpanzees by the fusogenic domain of HIV gp41 envelope protein.

The fusogenic (F) domain of human immunodeficiency virus (HIV) gp41 envelope (env) protein has sequence similarities to many virus and mediates the fusion of HIV-infected cells. During a survey of the immunogenicity of HIV env peptides in chimpanzees, we have observed that HIV peptide immunogenicity was dramatically altered by the NH2-terminal synthesis of the gp41 F domain to an otherwise immunogenic peptide. We compared two hybrid peptide types comprised of T helper (Th) and B cell epitopes of HIV gp120 env protein for their immunogenicity in chimpanzees. The Th-B epitope hybrid peptides contained the HIV gp120 Th cell determinant, T1 (amino acids [aa] 428-440)-synthesized NH2 terminal to gp120 V3 loop peptides, which contain B cell epitopes that induce anti-HIV-neutralizing antibodies (SP10IIIB [aa 303-321] and SP10IIIB [A] [aa 303-327]). The F-Th-B peptide contained the HIV gp41 F domain of HIVIIIB gp41 (aa 519-530)-synthesized NH2 terminal to the Th-B peptide. Whereas Th-B peptides were potent immunogens for chimpanzee antibody and T cell-proliferative responses, the F-Th-B peptide induced lower anti-HIV gp120 T and B cell responses. Moreover, immunization of chimpanzees with F-Th-B peptide but not Th-B peptides induced a significant decrease in peripheral blood T lymphocytes (mean decrease during immunization, 52%; p < 0.02). Chimpanzees previously immunized with F-Th-B peptide did not respond well to immunization with Th-B peptide with T or B cell responses to HIV peptides, demonstrating that the F-Th-B peptide induced immune hyporesponsiveness to Th and B HIV gp120 env determinants. These observations raise the hypothesis that the HIV gp41 env F domain may be a biologically active immunoregulatory peptide in vivo, and by an as yet uncharacterized mechanism, promotes primate immune system hyporesponsiveness to otherwise immunogenic peptides.

Amino Acid Sequence↗
PubMed1993

X-ray-crystallographic studies of complexes of pepstatin A and a statine-containing human renin inhibitor with endothiapepsin.

H-189, a synthetic human renin inhibitor, and pepstatin A, a naturally occurring inhibitor of aspartic proteinases, have been co-crystallized with the fungal aspartic proteinase endothiapepsin (EC 3.4.23.6). H-189 [Pro-His-Pro-Phe-His-Sta-(statyl)-Val-Ile-His-Lys] is an analogue of human angiotensinogen. Pepstatin A [Iva(isovaleryl)-Val-Val-Sta-Ala-Sta] is a blocked pentapeptide which inhibits many aspartic proteinases. The structures of the complexes have been determined by X-ray diffraction and refined to crystallographic R-factors of 0.15 and 0.16 at resolutions of 0.18 nm (1.8 A) and 0.2 nm (2.0 A) respectively. H-189 is in an extended conformation, in which the statine residue is a dipeptide analogue of P1 and P'1 as indicated by the conformation and network of contacts and hydrogen bonds. Pepstatin A has an extended conformation to the P'2 alanine residue, but the leucyl side chain of the terminal statine residue binds back into the S'1 subsite, and an inverse gamma-turn occurs between P'1 and P'3. The hydroxy moiety of the statine at P1 in both complexes displaces the solvent molecule that hydrogen-bonds with the catalytic aspartate residues (32 and 215) in the native enzyme. Solvent molecules originally present in the native structure at the active site are displaced on inhibitor binding (12 when pepstatin A binds; 16 when H-189 binds).

Amino Acid Sequence↗
PubMed1993

Demonstration of lipooligosaccharide immunotype and capsule as virulence factors for Neisseria meningitidis using an infant mouse intranasal infection model.

Using an infant mouse intranasal infection model, we have compared the virulence of 17 epidemiologically related isolates of Neisseria meningitidis associated with an outbreak of meningococcal disease in Gloucestershire, UK, and one German isolate. The isolates were all of serotype 15 subtype P1:7, 16 and were identical by restriction fragment length polymorphism analysis, but differed in either (i) whether they were isolated from a case or a carrier, (ii) the presence or absence of group B capsule, or (iii) their lipooligosaccharide (LOS) immunotype. The results indicate that capsule is a major virulence determinant and is required for colonization and hence for invasion. In addition, the LOS L3,7,9 immunotype, when compared to the L1,8,10 immunotype, is a secondary virulence factor which enhances colonization of nasal passages and invasion of the blood stream by both case and carrier isolates. Two case isolates which were unusual in possessing the L1,8,10 immunotype, established invasive infection, but this was associated with a switch to the L3,7,9 immunotype. The results confirm that LOS is a virulence factor for N. meningitidis and that immunotype L3,7,9 is associated with invasive disease.

Administration, Intranasal↗
PubMed1993

Haemophilus influenzae type b disease in north-west England.

A study was made in the north-west of England during 1989 in order to ascertain the incidence of serious Haemophilus influenzae infection, its short-term morbidity and certain characteristics of treatment. The incidence of culture-proven infection was 28 per 100,000 children under 5 years of age. Case fatality was 3%, one of the deaths being in a 6-year-old child. Some of the information obtained will help to assess the cost-effectiveness of the new vaccine to be administered to children in the U.K. The mean length of stay in hospital for all cases was 10 days. Of a total of 87 patients, 20 (23%) were admitted to an intensive therapy unit while five were transferred from a district general hospital to a regional paediatric unit. The estimated average cost per episode of acute care was 2700 pounds. Antibiotic regimens varied considerably.

Anti-Bacterial Agents↗
PubMed1993

Age incidence of meningococcal infection England and Wales, 1984-1991.

The age incidence of meningococcal infections occurring between 1984 and 1991 in England and Wales was determined from data submitted with isolates to the Meningococcal Reference Laboratory for England and Wales. The incidence was maximum at 6 months of age and thereafter declined sharply to the age of 4 years. It was followed by a small secondary peak at 17-18 years. There was a relative excess of group B infections in the early months of life and, although group B and group C infections both peaked at 6 months of age, the latter did not decline until after the age of 9 months. Certain strains of meningococci were more likely to be associated with disease in older children and young adults.

Adolescent↗
PubMed1993

Campylobacter bacteraemia in England and Wales, 1981-91.

Routine surveillance of infection in England and Wales detected 394 cases of campylobacter bacteraemia in 11 years. This represented an average incidence of 1.5 per 1000 intestinal campylobacter infections, with a range of 0.3/1000 in children aged 1-4 years to 5.9/1000 in patients aged 65 years or more. Definitive identification of 257 isolates showed that 89% were Campylobacter jejuni or C. coli; other species were C. fetus (8.6%), C. lari (0.8%), C. upsaliensis (0.8%), Helicobacter (Campylobacter) fennelliae (0.8%), and Helicobacter (Campylobacter) cinaedi (0.4%). Most (71%) of the C. jejuni/C. coli bacteraemias were in patients with acute enteritis. Of the patients with C. fetus bacteraemia only 27% had diarrhoea; they were older than patients with C. jejuni or C. coli bacteraemia (54.1 v. 45.9 years) and proportionally more of them were male (M:F ratio 2.7:1 v. 1.9:1); 41% had endovascular pathology or cellulitis. There was a higher proportion of C. jejuni serogroup O 4 (Penner) and O 18 strains among blood than faecal isolates, which suggests that they were unusually serum resistant and/or invasive.

Adolescent↗
PubMed1993

Current and future trends in immunization against meningitis.

The progress in vaccines for Haemophilus influenzae type b infection is followed; it is the disadvantages of pure polysaccharide vaccines that have stimulated the development of the present generation of polysaccharide-protein conjugated vaccines. From extensive clinical trials it is apparent that these are very effective in preventing disease in children. Conjugated haemophilus vaccines were introduced into the routine immunization schedules in the UK in Autumn 1992. Meningococcal A and C polysaccharide vaccines, effective for epidemic disease, are only now being developed in a protein conjugated form with the prospect of protecting young children and producing durable immunity. Group B outer membrane-based meningococcal vaccines produce only a low degree of protection and much further work is needed before even the optimum vaccine constituents of this organism can be identified. Vaccines to replace multivalent pneumococcal polysaccharide mixtures are only in the very earliest stages of development.

Bacterial Capsules↗
PubMed1993

Campylobacter jejuni adapts to aerobic metabolism in the environment.

Campylobacter jejuni, when left on blood agar for prolonged periods, was found to survive better in air than under micro-aerobic conditions. After a period of 2-3 days in air, all strains of C. jejuni examined grew freely in air on subculture, and could be further subcultured apparently indefinitely in air. This adaptation to aerobic metabolism was accompanied by a change in colony morphology and some changes in outer-membrane protein patterns, but no change in serotyping reactions. The ability to colonise mice was unaltered as was the helical morphology of growing cells. The important survival phase of C. jejuni, when outside the animal gut, involves not only a change to coccal morphology but also fundamental changes in the metabolism of the organism. These changes are likely to be relevant to techniques required for culturing C. jejuni from foods and environmental sources.

Adaptation, Physiological↗
PubMed1993

Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo controlled study in healthy volunteers.

1. Peak saccade velocity provides a valuable means of assessing the sedative effect of drugs in humans. The present study investigated the effects of zolpidem, an imidazopyridine hypnotic, on saccade velocity in healthy volunteers after single and repeated administration. 2. Zolpidem 5 mg, 10 mg and 20 mg significantly and dose dependently depressed peak saccade velocity during the 1.5 h after a single administration. On the morning after zolpidem administration, peak saccade velocity had returned towards pretreatment levels. Nitrazepam 10 mg also significantly depressed peak saccade velocity but the effect was maintained the following morning. The saccade response to zolpidem (5 and 10 mg) was undiminished after the seven nightly doses. 3. Nightly administration of zolpidem improved subjective sleep quality and there was no evidence of rebound insomnia following cessation of drug treatment.

Adult↗
PubMed1993

Disruption of visual short-term memory by changing-state auditory stimuli: the role of segmentation.

Typically, serial recall performance can be disrupted by the presence of an irrelevant stream of background auditory stimulation, but only if the background stream changes over time (the auditory changing-state effect). It was hypothesized that segmentation of the auditory stream is necessary for changing state to be signified. In Experiment 1, continuous random pitch glides failed to disrupt serial recall, but glides interrupted regularly by silence brought about the usual auditory changing-state effect. In Experiment 2, a physically continuous stream of synthesized vowel sounds was found to have disruptive effects. In Experiment 3, the technique of auditory induction showed that preattentive organization rather than critical features of the sound could account for the disruption by glides. With pitch glides, silence plays a preeminent role in the temporal segmentation of the sound stream, but speech contains correlated time-varying changes in frequency and amplitude that make silent intervals superfluous.

Acoustic Stimulation↗
PubMed1992

Meningococcal infections in England and Wales: 1991.

There were fewer reports of cases of meningococcal infection in England and Wales during 1991 than in 1990. The number of isolates received at the Meningococcal Reference Laboratory decreased by 102 (7%), largely due to fewer strains being received from South West Thames, North East Thames and North Western regions. Group C infections showed a greater decrease than group B, with 16% fewer strains reported in 1991 than in 1990. Eight per cent of the strains received during 1991 showed reduced susceptibility to penicillin (MIC > 0.16mg/l).

Adolescent↗
PubMed1992

The serum resistance of gonococci in the majority of urethral exudates is due to sialylated lipopolysaccharide seen as a surface coat.

Examined before subculture, gonococci in 18 urethral exudates collected from different patients were serum-resistant. For 15 exudates, the resistance was drastically reduced by treatment with neuraminidase and by one subculture on laboratory media. It was restored by incubation with cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA). Electron microscopic examination of gonococci in eight exudates showed a surface structure stained by Ruthenium red which disappeared in most samples when they were treated with neuraminidase. These results were identical with those of previous studies on in vitro grown gonococci which had shown that serum resistance is due to sialylation of a 4.5-kDa conserved component of gonococcal lipopolysaccharide (LPS) by host CMP-NANA, which masks the target site for bactericidal IgM and renders surface LPS stainable by Ruthenium red. The serum resistance of gonococci in the remaining three exudates was not reduced by neuraminidase nor by subculture. The mechanism of this stable resistance is unknown.

Blood Bactericidal Activity↗
PubMed1992

Wegener's granulomatosis masquerading as pancreatic carcinoma.

A 62-year-old male presented with painless jaundice and solitary pulmonary and pancreatic masses. An extensive evaluation revealed Wegener's granulomatosis as the etiology. His pancreatic mass and jaundice responded to temporary stenting and therapy with cyclophosphamide and prednisone. While pancreatic vasculitis in Wegener's granulomatosis has been noted previously in autopsy studies, symptomatic involvement has been reported only once previously and never as a presenting feature of the disease. The antineutrophil cytoplasmic antibody (ANCA) assay proved useful in establishing the diagnosis. Necrotizing vasculidities can mimic pancreatic carcinoma and should be considered in the differential diagnosis of atypical cases.

Antibodies, Antineutrophil Cytoplasmic↗